The overall objective of this laboratory is to understand the roles of the J chain and IgM polymerization in antibody biosynthesis. Polymeric antibodies might have been expected as a late development in the immune response to provide an amplification of biological function. Exactly the reverse appears to be true. Pentamer IgM is not only the first functional antibody to have evolved in primitive vertebrates, but it remains the first product of antigen stimulation in mammalian lymphocytes and the ablation of its synthesis results in the suppression of all subsequent IgG and IgA synthesis. This conservation of a polymeric species over evolutionary time and the even greater conservation observed for the polymer joining component, suggest that IgM polymerization is an integral step in the differentiation of the antibody-producing cell. The proposed research will, therefore, attempt to define the intracellular events leading to and following from pentamer synthesis and secretion. To achieve this aim, studies will be undertaken to clarify a) the relationships between antigen activation, J chain synthesis, and polymer assembly, b) the function of the secreted pentamer in the switchover to IgG synthesis, and c) the genetic control of J and heavy chain synthesis.